CAAT/Enhancer Binding Proteins Directly Modulate Transcription from the Peroxisome Proliferator- Activated Receptor γ2 Promoter

Clarke, Stephen; Robinson, Claudius E.; Gimble, Jeffrey M.

doi:10.1006/bbrc.1997.7627

Cited by 213 publications

(160 citation statements)

References 33 publications

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“…As positive control, C/EBPa binding to the same promoter region was detectable at day 4 and peaked at day 8 ( Figure 5b, left panel). As negative control, neither C/EBPa nor KLF9 could bind to the À2000-bp region of the PPARg2 promoter ( Figure 5b, right panel; Supplementary Table S1), which is in agreement with previous report that C/EBPa does not bind to the distal region of the PPARg2 promoter, 28 and our observation that KLF9 binds to the 0.6-kb proximal promoter region of PPARg2 (Figure 4). Taken together, the results indicate that KLF9 could directly bind to the promoter region of PPARg2 at the middle stage of 3T3-L1 adipocyte differentiation.…”

Section: Resultssupporting

confidence: 92%

Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis

et al. 2010

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Krü ppel-like factors (KLFs) as a family of zinc-finger transcription factors involve in the regulation of many physiological processes. In these studies, KLF9 was characterized for its role in adipogenesis. The expression of KLF9 was markedly upregulated during the middle stage of 3T3-L1 adipocyte differentiation, and inhibition of KLF9 by RNAi impaired adipogenesis. Using promoter deletion and mutation analysis, we identified two KLF9-binding sites within the 0.6-kb region of the PPARc2 proximal promoter, indicating that KLF9 interacts with the PPARc2 promoter. Furthermore, we found that KLF9 could synergistically activate PPARc2 promoter by directly interacting with C/EBPa. In addition, overexpression of PPARc2 rescued the impairment of adipocyte differentiation induced by KLF9 knockdown, which supports that PPARc2 is a downstream target of KLF9. Collectively, our results indicate KLF9 as a key pro-adipogenic transcription factor through regulation of PPARc2 expression with C/EBPa at the middle stage of adipogenesis.

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Section: Resultssupporting

confidence: 92%

Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis

et al. 2010

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“…Previous studies (7,11) revealed that C͞EBP␤, a key transcriptional activator of the C͞EBP␣ and PPAR␥ genes (7,(12)(13)(14)(15), is expressed immediately upon treatment of preadipocytes with differentiation inducers (11). However, acquisition of DNA-binding function by C͞EBP␤ is delayed until 12-16 h after induction (11).…”

Section: Resultsmentioning

confidence: 99%

“…The time at which DNA-binding activity (measured in vitro) is acquired by C͞EBP␤ corresponds exactly to the time at which it associates with centromeres through binding sites on centromeric satellite DNA ex vivo (11). Having acquired DNA-binding function, C͞EBP␤ transcriptionally activates both the C͞EBP␣ and PPAR␥ genes through C͞EBP regulatory elements in their proximal promoters (12)(13)(14)(15). The preadipocytes exit the cell cycle after they have undergone approximately two rounds of mitosis, i.e., MCE.…”

mentioning

confidence: 97%

Mitotic clonal expansion: A synchronous process required for adipogenesis

Tang

Otto

Lane

2002

Proc. Natl. Acad. Sci. U.S.A.

728

654

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When induced to differentiate, growth-arrested 3T3-L1 preadipocytes synchronously reenter the cell cycle and undergo mitotic clonal expansion (MCE) followed by expression of genes that produce the adipocyte phenotype. The preadipocytes traverse the G1͞S checkpoint synchronously as evidenced by the expression͞ activation of cdk2-cyclin-E͞A, turnover of p27͞kip1, hyperphosphorylation of Rb, translocation of cyclin D1 from nuclei to cytoplasm and GSK-3␤ from cytoplasm to nuclei, and incorporation of [ 3 H]thymidine into DNA. As the cells cross the G1͞S checkpoint, C͞EBP␤ acquires DNA-binding activity, initiating a cascade of transcriptional activation that culminates in the expression of adipocyte proteins. The mitogen-activated protein kinase͞extra-cellular signal-regulated kinase kinase (MEK) inhibitor PD98059 delays, but does not block, MCE and differentiation, the extent of the delay causing a comparable delay in the expression of cell-cycle markers, MCE, and adipogenesis. The more potent and specific MEK inhibitor UO126 and the cyclin-dependent kinase inhibitor roscovitine, which inhibit the cell cycle at different points, block MCE, expression of cell cycle and adipocyte markers, as well as adipogenesis. These results show that MCE is a prerequisite for differentiation of 3T3-L1 preadipocytes into adipocytes.cell cycle ͉ adipogenesis ͉ 3T3-L1 preadipocyte ͉ C͞EBP␣ ͉ PPAR␥

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“…To dissect finely the specific molecular action of SRC-3 in adipocyte differentiation, we examined the impact of SRC-3 on a crucial checkpoint for the adipogenic program, that is, the control of expression of the PPAR␥2 gene (11,12). During fat-cell differentiation, the expression of PPAR␥2 is subject to control by transcription factors such as C͞EBP, the E2Fs, and Kruppel-like factor 5 (13)(14)(15). Based on these prior observations, we tested the transcriptional impact of SRC-3 on an artificial reporter plasmid containing multimerized C͞EBP binding sites.…”

Section: Adipogenesis Is Severely Impaired In the Absence Of Src-3 Andmentioning

confidence: 99%

Oncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program

Louet¹,

Coste

Amazit³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

104

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The white adipocyte is at the center of dysfunctional regulatory pathways in various pathophysiological processes, including obesity, diabetes, inflammation, and cancer. Here, we show that the oncogenic steroid receptor coactivator-3 (SRC-3) is a critical regulator of white adipocyte development. Indeed, in SRC-3 ؊/؊ mouse embryonic fibroblasts, adipocyte differentiation was severely impaired, and reexpression of SRC-3 was able to restore it. The early stages of adipocyte differentiation are accompanied by an increase in nuclear levels of SRC-3, which accumulates to high levels specifically in the nucleus of differentiated fat cells. Moreover, SRC-3 ؊/؊ animals showed reduced body weight and adipose tissue mass with a significant decrease of the expression of peroxisome proliferator-activated receptor ␥2 (PPAR␥2), a master gene required for adipogenesis. At the molecular level, SRC-3 acts synergistically with the transcription factor CAAT͞enhancer-binding protein to control the gene expression of PPAR␥2. Collectively, these data suggest a crucial role for SRC-3 as an integrator of the complex transcriptional network controlling adipogenesis.adipogenesis ͉ peroxisome proliferator-activated receptor (PPAR) ͉ transcription ͉ coregulators ͉ metabolism

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CAAT/Enhancer Binding Proteins Directly Modulate Transcription from the Peroxisome Proliferator- Activated Receptor γ2 Promoter

Cited by 213 publications

References 33 publications

Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis

Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis

Mitotic clonal expansion: A synchronous process required for adipogenesis

Oncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program

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